Electroporation (“EP”) originated for in vitro transfection (Neumann et al., 1982) and over the past 25 years has become a standard laboratory method. The administration of electric fields at specific pulse conditions increases cell membrane permeability, which allows uptake of molecules through the cell membrane. The initial demonstration of in vivo electroporation was the delivery of chemotherapeutic agents to solid tumors (Okino et al. 1991). In the mid to late 1990's, the effectiveness of this approach for drug delivery was demonstrated in a variety of different tumors in animals and humans (Gotheif et al, 2003). This technique was then tested for enhanced plasmid DNA delivery (Holler et al., 1996; Nishi et al, 1996). In vivo electroporation is theoretically applicable to all tissues tested. A principal issue limiting the use of in vivo electroporation has been the accessibility of the particular tissue for the application of the electric field. The use of in vivo electroporation for plasmid DNA deliver has seen tremendous growth, including the initiation of the first clinical trials.
Treatment of the tissue site by localized delivery of the therapeutic agent coupled with focused delivery of the electroporation signal facilitates selective application of the treatment to the target tissue sought to be treated. In this manner surrounding tissue is spared the adverse effects of treatment while the targeted tissue receives enhanced more optimal levels of the agent.
Plasmid DNA-based gene transfer is attractive because it eliminates the need for a biological vector. Application of plasmid DNA-based gene transfer has been handicapped by the lack of efficient and/or effective delivery methods. When compared to viral delivery, the advantages of plasmid DNA-based gene transfer include reduced potential for immunogenicity, integration into the genome, and environmental spread. One method that has emerged as a means to facilitate delivery of plasmid DNA is in vivo electroporation or electropermeabilization.